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Combinatorial Therapeutic Effect of Inhibitors of Aldehyde Dehydrogenase and Mitochondrial Complex I, and the Chemotherapeutic Drug, Temozolomide against Glioblastoma Tumorspheres

DC Field Value Language
dc.contributor.author강석구-
dc.contributor.author김의현-
dc.contributor.author문주형-
dc.contributor.author박현호-
dc.contributor.author장종희-
dc.date.accessioned2021-04-29T16:47:37Z-
dc.date.available2021-04-29T16:47:37Z-
dc.date.issued2021-01-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/182022-
dc.description.abstractResident cancer cells with stem cell-like features induce drug tolerance, facilitating survival of glioblastoma (GBM). We previously showed that strategies targeting tumor bioenergetics present a novel emerging avenue for treatment of GBM. The objective of this study was to enhance the therapeutic effects of dual inhibition of tumor bioenergetics by combination of gossypol, an aldehyde dehydrogenase inhibitor, and phenformin, a biguanide compound that depletes oxidative phosphorylation, with the chemotherapeutic drug, temozolomide (TMZ), to block proliferation, stemness, and invasiveness of GBM tumorspheres (TSs). Combination therapy with gossypol, phenformin, and TMZ induced a significant reduction in ATP levels, cell viability, stemness, and invasiveness compared to TMZ monotherapy and dual therapy with gossypol and phenformin. Analysis of differentially expressed genes revealed up-regulation of genes involved in programmed cell death, autophagy, and protein metabolism and down-regulation of those associated with cell metabolism, cycle, and adhesion. Combination of TMZ with dual inhibitors of tumor bioenergetics may, therefore, present an effective strategy against GBM by enhancing therapeutic effects through multiple mechanisms of action.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherMDPI-
dc.relation.isPartOfMOLECULES-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAldehyde Dehydrogenase / antagonists & inhibitors*-
dc.subject.MESHAldehyde Dehydrogenase / metabolism-
dc.subject.MESHAntineoplastic Combined Chemotherapy Protocols / pharmacology*-
dc.subject.MESHBrain Neoplasms* / drug therapy-
dc.subject.MESHBrain Neoplasms* / enzymology-
dc.subject.MESHElectron Transport Complex I / antagonists & inhibitors*-
dc.subject.MESHElectron Transport Complex I / metabolism-
dc.subject.MESHEnzyme Inhibitors / pharmacology-
dc.subject.MESHGlioblastoma* / drug therapy-
dc.subject.MESHGlioblastoma* / enzymology-
dc.subject.MESHHumans-
dc.subject.MESHNeoplasm Proteins / antagonists & inhibitors*-
dc.subject.MESHNeoplasm Proteins / metabolism-
dc.subject.MESHSpheroids, Cellular / enzymology*-
dc.subject.MESHTemozolomide / pharmacology-
dc.titleCombinatorial Therapeutic Effect of Inhibitors of Aldehyde Dehydrogenase and Mitochondrial Complex I, and the Chemotherapeutic Drug, Temozolomide against Glioblastoma Tumorspheres-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Neurosurgery (신경외과학교실)-
dc.contributor.googleauthorHun Ho Park-
dc.contributor.googleauthorJunseong Park-
dc.contributor.googleauthorHye Joung Cho-
dc.contributor.googleauthorJin-Kyoung Shim-
dc.contributor.googleauthorJu Hyung Moon-
dc.contributor.googleauthorEui Hyun Kim-
dc.contributor.googleauthorJong Hee Chang-
dc.contributor.googleauthorSoo Youl Kim-
dc.contributor.googleauthorSeok-Gu Kang-
dc.identifier.doi10.3390/molecules26020282-
dc.contributor.localIdA00036-
dc.contributor.localIdA00837-
dc.contributor.localIdA01383-
dc.contributor.localIdA01750-
dc.contributor.localIdA03470-
dc.relation.journalcodeJ03201-
dc.identifier.eissn1420-3049-
dc.identifier.pmid33429981-
dc.subject.keywordaldehyde dehydrogenase-
dc.subject.keywordbioenergenetics-
dc.subject.keywordglioblastoma-
dc.subject.keywordoxidative phosphorylation-
dc.subject.keywordtemozolomide-
dc.subject.keywordtumorsphere-
dc.contributor.alternativeNameKang, Seok Gu-
dc.contributor.affiliatedAuthor강석구-
dc.contributor.affiliatedAuthor김의현-
dc.contributor.affiliatedAuthor문주형-
dc.contributor.affiliatedAuthor박현호-
dc.contributor.affiliatedAuthor장종희-
dc.citation.volume26-
dc.citation.number2-
dc.citation.startPage282-
dc.identifier.bibliographicCitationMOLECULES, Vol.26(2) : 282, 2021-01-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers

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